Evidence from numerous laboratories including our own suggests that there is a relationship between the presence of estrogen receptors in breast cancer and a patient's response to endocrine manipulation. Current techniques of estrogen receptor analysis require sophisticated equipment, large amounts of tissue and a great deal of laboratory time. These factors limit the application of these methods to large lesions thereby denying many patients the benefit of this valid prognostic index. Additionally, only a few centers will have the necessary equipment and expertise to perform estrogen receptor analyses thus inconveniencing the patient and clinician as well as limiting the availability of the study. We have developed estrogens with fluorescent labels which qppear to interact specifically with receptors in the cytoplasm of hormonally responsive tissues and undergo subsequent translocation into nuclei. We propose to develop a sensitive, simple and direct method of determining estogen receptor activity in hormonally dependent cancers as well as in normal target tissues such as endometrium and mammary gland. This approach, direct visualization of fluorescent hormone uptake and intracellular migration, provides additional information regarding the intactness of the hormone response mechanism. We will correlate both the intracellular distribution and quantitative measurements of receptor activity using fluorescent labeled steroid hormones with that observed using established procedures of tritium-labeled steroid ligands. These receptor data on small tissue biopsies will be related to the endocrine status and clinical response of the patient to hormonal manipulation.